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Changes in neuronal response to ischemia in retinas with genetic alterations of somatostatin receptor expression
Author(s) -
Catalani Elisabetta,
Cervia Davide,
Martini Davide,
Bagnoli Paola,
Simonetti Elisa,
Timperio Anna Maria,
Casini Giovanni
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05419.x
Subject(s) - somatostatin receptor , retina , glutamate receptor , biology , retinal , receptor , endocrinology , medicine , ischemia , excitotoxicity , somatostatin , microbiology and biotechnology , neuroscience , biochemistry
Ischemia is a primary cause of neuronal death in retinal diseases. The repertoire of expressed transmitter receptors would determine the neurons' responses to ischemic damage, and peptidergic receptors may be involved. With a new in vitro model of the ischemic mouse retina, we investigated whether an altered expression of somatostatin receptors could modulate retinal responses to ischemia. We used retinas of somatostatin receptor 1 (sst 1 ) knock out (KO) mice, where sst 2 are over‐expressed and over‐functional, and of sst 2 KO mice. TUNEL analysis of ischemic retinas showed a marked reduction of cell death in sst 1 KO retinas, while there were no differences between wild‐type (WT) and sst 2 KO retinas. In addition, caspase‐3 mRNA expression was also reduced in sst 1 KO as compared to WT retinas. An immunohistochemical analysis demonstrated that different cell populations responded differently to the ischemic insult, and that the persistence of some immunohistochemical markers was greater in sst 1 KO than in WT or in sst 2 KO retinas. In particular, rod bipolar cell survival was markedly improved in sst 1 KO retinas, while it was dramatically decreased in sst 2 KO retinas. Furthermore, consistent with a role of glutamate excitotoxicity in ischemia‐induced neuronal death, retinal glutamate release was observed to increase under ischemic conditions, but this increase was significantly reduced in sst 1 KO retinas. These observations demonstrate that an increased presence of functional sst 2 protects against retinal ischemia, thus implementing the background for the use of sst 2 analogs in therapies of retinal diseases such as glaucoma or diabetic retinopathy.